Works in Progress

You'll get no kick from cocaine if you take this new vaccine

You know the feeling. It sends you to the minimart at midnight for chips, makes you down a pint of ice cream in seconds, destroys your promise to lay off the caffeine and cigarettes. Maybe it's a video game you can't stop playing or a shopping mall that seems to swallow your wallet. An out-of-control craving, a mindless compulsion, an irrepressible urge. Drug abusers call it jonesing.

But experienced addicts will tell you that you don't really know what jonesing is all about until you've tried crack. Smoked cocaine is probably the most addictive substance used by humankind. Its effects are so potent and immediatecrack reaches the brain within 20 heartbeats of inhalationthat a single hit can hook you.

And once you're hooked, you're cooked. There's no approved medical treatment for cocaine addiction: no therapeutic equivalent of the methadone dose, the Antabuse pill, or the nicotine patch. Instead there are rehab centers, Narcotics Anonymous meetings, a shrink in the afternoon, group therapy at night. And the success rates of these programs are sobering in themselves. Most people in talk therapy for cocaine addiction, for example, are still using. At a typical long-term treatment center, only 25 of every 100 residents are still completely clean three to five years after they leave.

To beat those odds, the National Institute on Drug Abuse has made developing an effective treatment for cocaine addiction a top priority. The institute has 38 different medications in clinical trials across the country. Most are high-tech antidotes that seek to alter the subtle and complex brain chemistry governing addiction: a chemistry that may be common to cravings for coffee, cigarettes, or cr?me caramel. The institute's strategy is based on the view that addiction is a disease to be cured rather than a simple failure of will or judgment.

And at Daytop, a residential treatment facility run by the Apt Foundation in Newtown, Connecticut, the institute is testing a time-honored approach to controlling disease: vaccination. Several dozen addicts housed in Daytop's gloomy brick barracks on the abandoned grounds of a state mental hospital have pledged to forgo their cocaine habit and shoot up an experimental vaccine instead. The cocaine vaccine works the same way other vaccines do: by stimulating the immune system to produce antibodies that bind to a foreign entity, preventing it from entering the brain or otherwise interacting with the body's organs and tissues. In this case, the foreigner isn't a virus like polio or a toxin like the one that causes lockjaw. It's another drug.

The vaccine's developerschemists at ImmuLogic Pharmaceutical in Waltham, Massachusettsdon't plan to vaccinate the masses to prevent cocaine addiction. Their goal instead is to help people who are already addicted. Cocaine itself escapes the body's defenses because its molecule (C17H21NO4) is too small to activate the immune system. The vaccine couples a piece of the cocaine molecule to chemical carriers that slow its release into the bloodstream and make it large enough to be recognized. Once the immune system is thus primed, the use of cocainevia nose, lung, or veinshould prompt legions of antibodies to enter the bloodstream and ambush the drug. In theory, the vaccinated user will no longer get a cocaine high.

And in practice, vaccinated users do seem to lose all interest in their habit. But so far those users are cocaine-addicted rats. ImmuLogic studies show that a typical rat junkie will press a bar repeatedly to load cocaine into its IV line. A vaccinated rat junkie, in contrast, becomes indifferent to the dose bar. The vaccine's creators expect more modest results in humans.

"It's not something that will be a panacea for all [cocaine] addicts," says John Shields, senior vice president of research at Cantab Pharmaceuticals, a British company that recently bought ImmuLogic's vaccine program. "It's only going to be useful if an individual actually wants to give it up."

That's because there's a catch to the treatment the rats can't tell you about: the vaccine doesn't reduce the jonesing. Drug craving is thought to be created by as-yet-unidentified changes in the function and perhaps even the structure of the brain. And it's the cravingthe compulsion to use the drug despite its adverse consequencesthat's the essence of addiction. Whether using or not, an addict who's craving isn't cured.

"It started after my first trylike a runaway roller coaster," says David, a Daytop resident. With a stocky build and a youthful, snaggletoothed smile, he could easily pass for a college football player or wrestler. But David left college in his early twenties and picked up a 15-year habit interrupted only by visits to prison. He agreed to be in the trial, he says, because the prospect of a cure intrigued him. "If it's something that might stop this madness or make it preventable, you know? I'm for it."

Another resident, Jeff, says he's in the trial "for the money." Participants receive $150 for each of three shots administered over the course of three months. "Say I was to use cocaine and I didn't get high," says Jeff. "Being an addict, I would move on to something else that would get me off. You'd need a vaccine for all the drugs for it to work."

The change-up, of course, is a possibility experts have considered. Shields and his colleagues emphasize that the vaccine would only be suitable for people determined to stay clean and confront the psychological and behavioral aspects of addiction. Because the initial injections are unlikely to confer lifelong immunity, patients would have to be motivated enough to continue getting boosters, probably at least once a year.

"I think the vaccine will be very helpful for people who have a desire to stop using, so that if they slip and use once, they won't get much out of it," says Tom Kosten, a professor of psychiatry at the Yale School of Medicine and head of the vaccine trials. Relapses are the reason most treatment programs fail, he says, because a single, brief exposure to a disavowed drug ignites a compulsion in addicts more powerful than that engendered by continual use. "The most potent stimulus for craving is actually to use a little bit of the drug. Substance abusers will tell you exactly the opposite: they think that if they just got a little bit they'd feel better. But they don't. They feel very good for a minute, then they feel deprived."

It's that rapid cycling of euphoria and deprivation that makes cocaine dangerous. The biology of addiction is not entirely understood, but it seems that the faster a drug's effects build and diminish, the more compulsion it creates. That's why crack cocaine is more addictive than snorted cocaine: inhaling into the lungs' large surface area rather than the mucous membranes of the nose gets the drug into the bloodstream much faster. In fact, the speed and potency of cocaine's assault on the body could pose a major challenge to the vaccine approach. It took researchers years to learn how to build an antibody response that could counter the drug, and even a strongly fortified immune system may not defeat it completely.

"For people who want to keep using, I'm sure the vaccine can be overridden by just lots of use," says Kosten. Alan Leshner, head of the National Institute on Drug Abuse, agrees. "You can't compare this directly with, you know, the polio vaccine. Nobody wants polio, so you're not trying to override the vaccine. But people love cocaine. We don't know what will happen if you take six times the amount you'd usually use to try to get high."

But one trial participant says he does know. He left Daytop after receiving all three shots and immediately started injecting megahits of cocaine with a lady friend over the course of a weekendto no avail. This report is, of course, what scientists call anecdotal evidence from an unreliable source. And the current trials are measuring the vaccine's safety at different dosages, not its effectiveness. Nevertheless, in subsequent stages of testing, subjective accounts will become a crucial part of the clinical data.

Some researchers remain skeptical of the vaccine approach because it doesn't treat the underlying physiology of addiction. Cocaine is thought to work its seduction in part by transiently increasing levels of a nerve-signaling substance called dopamine, which communicates feelings of pleasure in the brain. Imaging studies by Nora Volkow, head of the medical department at Brookhaven National Laboratory in Upton, New York, revealed that the brains of cocaine addicts release half as much dopamine as substance-free subjects. Whether this depletion is a cause or a consequence of drug use isn't clear, she says. But she contends that medications must be developed to help restore normal dopamine function in substance abusers.

"[The vaccine] will prevent the reinforcing aspects of the drug," Volkow explains. "And then what we may need is a medication for the first two weeks of abstinence, when you want to really decrease intense craving. And then we may need something else that enhances dopamine once the craving goes away."

That pharmacopoeia should warm the hearts of pill-poppers and producers everywhere. But so far no drug has proven effective in treating any aspect of cocaine addiction. And according to Shields, it will take at least four years for the vaccine to complete clinical trials and be approved for marketing by the Food and Drug Administration.

Then it will have to win the approval of another group of skeptics: heavy cocaine users who are trying to quit. "A drug's not going to make people stop using other drugs," says Jeff, with the tired shrug of a man who's been fed one too many lines.